Variant 7-103498280-TAAAAA-TA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005045.4(RELN):c.8668-32_8668-29delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,600,952 control chromosomes in the GnomAD database, including 15,299 homozygotes. Variant has been reported in ClinVar as Likely benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.10 ( 1025 hom., cov: 31)

Exomes 𝑓: 0.13 ( 14274 hom. )

Consequence

RELN
NM_005045.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.463

Variant links:

Genes affected

RELN (HGNC:9957): (reelin) This gene encodes a large secreted extracellular matrix protein thought to control cell-cell interactions critical for cell positioning and neuronal migration during brain development. This protein may be involved in schizophrenia, autism, bipolar disorder, major depression and in migration defects associated with temporal lobe epilepsy. Mutations of this gene are associated with autosomal recessive lissencephaly with cerebellar hypoplasia. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

RELN links:

SLC26A5-AS1 (HGNC:):

SLC26A5-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 7-103498280-TAAAA-T is Benign according to our data. Variant chr7-103498280-TAAAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 259616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-103498280-TAAAA-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
RELN	NM_005045.4 linkuse as main transcript	c.8668-32_8668-29delTTTT	intron_variant	ENST00000428762.6	NP_005036.2	P78509-1
RELN	NM_173054.3 linkuse as main transcript	c.8668-32_8668-29delTTTT	intron_variant		NP_774959.1	P78509-2
SLC26A5-AS1	NR_110141.1 linkuse as main transcript	n.1366-6120_1366-6117delAAAA	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6 linkuse as main transcript	c.8668-32_8668-29delTTTT		intron_variant		5	NM_005045.4	ENSP00000392423.1		P78509-1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15540

AN:

151952

Hom.:

1026

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0274

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.104

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0474

Gnomad FIN

AF:

0.150

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.148

Gnomad OTH

AF:

0.122

GnomAD3 exomes

AF:

0.104

AC:

26133

AN:

250102

Hom.:

1788

AF XY:

0.106

AC XY:

14357

AN XY:

135296

show subpopulations

Gnomad AFR exome

AF:

0.0239

Gnomad AMR exome

AF:

0.0731

Gnomad ASJ exome

AF:

0.129

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0500

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.148

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.133

AC:

192196

AN:

1448882

Hom.:

14274

AF XY:

0.130

AC XY:

94132

AN XY:

721666

show subpopulations

Gnomad4 AFR exome

AF:

0.0224

Gnomad4 AMR exome

AF:

0.0782

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0511

Gnomad4 FIN exome

AF:

0.137

Gnomad4 NFE exome

AF:

0.150

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.102

AC:

15534

AN:

152070

Hom.:

1025

Cov.:

AF XY:

0.100

AC XY:

7460

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0273

Gnomad4 AMR

AF:

0.104

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0474

Gnomad4 FIN

AF:

0.150

Gnomad4 NFE

AF:

0.148

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.0745

Hom.:

119

Bravo

AF:

0.0969

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BranchPoint Hunter

6.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over